Methylamine → N-Cyclopropyl-4-methyl-3-(3-(1-(2-(2-(methylamino)ethoxy)phenyl)cyclopropylamino)-2-oxopyrazin-1(2H)-yl)benzamide

HRID 1697319Notes

Reaction equation

Cl[CH2:2][CH2:3][O:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[C:11]1([NH:14][C:15]2[C:16](=[O:34])[N:17]([C:21]3[CH:22]=[C:23]([CH:30]=[CH:31][C:32]=3[CH3:33])[C:24]([NH:26][CH:27]3[CH2:29][CH2:28]3)=[O:25])[CH:18]=[CH:19][N:20]=2)[CH2:13][CH2:12]1.[CH3:35][NH2:36]>C(O)C>[CH:27]1([NH:26][C:24](=[O:25])[C:23]2[CH:30]=[CH:31][C:32]([CH3:33])=[C:21]([N:17]3[CH:18]=[CH:19][N:20]=[C:15]([NH:14][C:11]4([C:6]5[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=5[O:4][CH2:3][CH2:2][NH:36][CH3:35])[CH2:13][CH2:12]4)[C:16]3=[O:34])[CH:22]=2)[CH2:29][CH2:28]1

Participants

Conditions

Temperature: 100 °C

Procedure

To 3-(3-(1-(2-(2-Chloroethoxy)phenyl)cyclopropylamino)-2-oxopyrazin-1(2H)-yl)-N-cyclopropyl-4-methylbenzamide (Example 167e, 100 mg) in a 10 mL microwave vial was added methylamine (2 mL of a 33% solution in ethanol). This was sealed and heated within a CEM Discover microwave for 30 min at 100° C. The volatiles were removed in vacuo and the residue taken up in methanol and purified by preparative HPLC (ACE column, 0.1% TFA:acetonitrile eluent) afforded the title compound. This was dissolved in acetonitrile and filtered through SCX resin eluting with acetonitrile and methanol (discarded) followed by 7N NH3 in methanol. The basic fractions were collected and the volatiles were removed in vacuo. Trituration with diethyl ether afforded the title product as a white solid (46 mg).

Workup

customThis was sealed
customThe volatiles were removed in vacuo
custompurified by preparative HPLC (ACE column, 0.1% TFA:acetonitrile eluent)

Sources & evidence

ORD record: ord-10b48e64b8f5417f8c711c14c4a21292
Source dataset: uspto-grants-2012_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08163905B2

Reaction notes

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